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Biomedical subjects

H Olausson

Publications and source records attributed to H Olausson.

At least 19 recordsLinked to original sources

Feelings of warmth correlate with neural activity in right anterior insular cortex.

The neural coding of perception can differ from that for the physical attributes of a stimulus. Recent studies suggest that activity in right anterior insular cortex may underlie thermal perception, particularly that of cold. We now examine whether this region is also important for the perception of warmth. We applied cutaneous warm stimuli on the left leg (warmth) in normal subjects (n = 7) during functional magnetic resonance imaging (fMRI). After each stimulus, subjects rated their subjective intensity of the stimulus using a visual analogue scale (VAS), and correlations were determined between the fMRI signal and the VAS ratings. We found that intensity ratings of warmth correlated with the fMRI signal in the right (contralateral to stimulation) anterior insular cortex. These results, in conjunction with previous reports, suggest that the right anterior insular cortex is important for different types of thermal perception.

Brain↗

Tactile functions after cerebral hemispherectomy.

Patients that were hemispherectomized due to brain lesions early in life sometimes have remarkably well-preserved tactile functions on their paretic body half. This has been attributed to developmental neuroplasticity. However, the tactile examinations generally have been fairly crude, and subtle deficits may not have been revealed. We investigated monofilament detection and three types of tactile directional sensibility in four hemispherectomized patients and six healthy controls. Patients were examined bilaterally on the face, forearm and lower leg. Normal subjects were examined unilaterally. Following each test of directional sensibility, subjects were asked to rate the intensity of the stimulation. On the nonparetic side, results were almost always in the normal range. On the paretic side, the patients' capacity for monofilament detection was less impaired than their directional sensibility. Despite the disturbed directional sensibility on their paretic side the patients rated tactile sensations evoked by the stimuli, on both their paretic and nonparetic body halves, as more intense than normals. Thus, mechanisms of plasticity seem adequate for tactile detection and intensity coding but not for more complex tactile functions such as directional sensibility. The reason for the high vulnerability of tactile directional sensibility may be that it depends on spatially and temporally precise afferent information processed in a distributed cortical network.

Adult↗

Long-term modulation by postnatal oxytocin of the alpha 2-adrenoceptor agonist binding sites in central autonomic regions and the role of prenatal stress.

The aim of this work was to evaluate whether oxytocin administered in male rats subcutaneously early in life in the absence or presence of food restriction during pregnancy has life-long effects on the alpha(2)-agonist binding sites in the nucleus of the solitarii tract (NTS), in the hypothalamus and the amygdala, as evaluated by quantitative receptor autoradiography. Maternal food restriction alone increased the affinity of the alpha(2)-agonist [(3)H]UK14.304 binding sites exclusively in the NTS. In offspring from ad libitum fed dams, oxytocin treatment significantly increased the density of alpha(2)-agonist binding sites in the NTS and in the hypothalamus. The K(d) value of the alpha(2)-agonist binding sites in the hypothalamus of these rats, but not in the other regions studied, was also significantly increased. In offspring from food-restricted dams, oxytocin treatment produced a significant increase of the B(max) values in the hypothalamus and the amygdala and the K(d) value of the alpha(2)-agonist binding sites in the NTS of these rats also was selectively and significantly increased. These results suggest that a postnatal, oxytocin-induced increase of regional alpha(2)-adrenoceptor function can be seen in adulthood by a persistent, regionally selective increase in the density of central alpha(2)-adrenoceptor agonist binding sites, in the absence of an affinity change in the NTS. Such a regional increase of alpha(2)-adrenoceptor signalling in adulthood may contribute to the anti-stress action of postnatal oxytocin. By contrast, after prenatal stress, the potential increase in alpha(2)-adrenoceptor signalling takes place via selective increases of density with no changes of affinity of the alpha(2)-agonist binding sites in the hypothalamus and the amygdala.

Adrenergic alpha-2 Receptor Agonists↗

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.

Adult↗

Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tIssues from guinea pigs.

The insulin-like growth factor (IGF) system is subjected to pregnancy-associated changes in the circulation and is suggested to be of importance for partitioning of nutrients between the mother and the foetus. Interestingly, maternal undernutrition alters the pregnancy-associated changes, with possible adverse consequences for the mother and the foetus. However, it is not known how malnutrition and pregnancy alter the expression of mRNA for IGFs locally in different tIssues. The aims of this study were to investigate where IGF-I and IGF-II are expressed in guinea pigs and how this expression is altered during food restriction and pregnancy. Ad libitum-fed and food-restricted (fed 70% of the ad libitum-fed intake four weeks before pregnancy and throughout the study) guinea pigs were mated. On day 40 of pregnancy and on the corresponding day for virginal females the animals were killed. mRNA for IGF-I and IGF-II was analysed in various organs/tIssues by solution hybridisation. mRNA for IGF-I was expressed in high amounts in uterus, liver and adipose tIssues. The expression was not affected by food restriction, but was increased in liver and adipose tIssue and decreased in uterus by pregnancy. mRNA for IGF-II was expressed in high amounts in the placenta and liver. In the placenta the expression was decreased by food restriction. Pregnancy increased the levels of mRNA for IGF-II in the liver. Food-restricted dams had smaller foetuses and placentas. In conclusion, this study indicates an important role for the adipose tIssue during gestation, not only as an energy store but also as an endocrine tIssue expressing IGF-I. The decreased expression of IGF-II in the placenta due to food restriction is suggested to have adverse effects on placental structure and function.

Animals↗

Unmyelinated tactile afferents signal touch and project to insular cortex.

There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.

Adult↗

Tactile directional sensibility and diabetic neuropathy.

Five different procedures used to diagnose neuropathy were compared in a "blind" study with diabetic patients. The aim was to evaluate tests of tactile directional sensibility. Three matched groups were examined, two groups with type I diabetes, either with or without suspected neuropathy, and one of healthy controls. Testing consisted of: (1) examination by a specialist in neurology, (2) electrophysiologic measurement of nerve conduction velocity and determination of cool sensitivity, and (3) determination of directional sensibility in two stages, with categorical and quantitative techniques. Abnormal test results were obtained for both groups of diabetic patients. Quantitatively measured directional sensibility had the highest sensitivity (89%) and specificity (85%) when calculated for patients who had received a diagnosis of neuropathy from the neurologist, despite one case of abnormal directional sensibility among the healthy controls. Conduction velocity testing was almost comparably sensitive (80%) and cool sensitivity, comparably specific (85%) when calculated in the same manner.

Adult↗

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Adult↗

Cortical activation by tactile and painful stimuli in hemispherectomized patients.

Hemispherectomized patients are able to perceive tactile and painful stimuli on their nonparetic as well as paretic body halves. We have used functional MRI to study the cortical mechanisms underlying this preserved somatosensory capacity. Nonpainful brushing and painful heat were applied to the skin of the legs in four hemispherectomized patients and, for comparison, in four normal subjects. Cortical activation was studied with a 1.5 T scanner using a BOLD (blood oxygen level dependent) protocol. All patients rated both the brushing and the heat pain as almost equally intense on each leg and the ratings were similar to those in normals. Brushing on the nonparetic leg activated primary and secondary somatosensory cortices (S1 and S2) in all patients, similar to findings in normals. Brushing on the paretic leg activated S1 in two patients and S2 in one of these patients. Heat pain activated S2, insular cortex and anterior cingulate cortex to a similar degree for both legs, but the activation was weaker in the patients than in the normals. For the individual patient, there was generally no obvious correlation between cortical activation as studied with the BOLD technique and psychophysical performance. The findings from tactile stimulation of the nonparetic leg, that the activation was similar to the contralateral activation in normals, suggest that tactile information processing in the hemisphere contralateral to the stimulation is independent of the corpus callosum. In contrast, the pain activation for the nonparetic leg was weaker than in normals, suggesting that pain activation in the hemisphere contralateral to the stimulation is dependent on transcallosal information processing. The latter finding was corroborated by a subnormal capacity for pain localization on the nonparetic foot in two of the patients. The findings from stimulation of the paretic leg show that areas typically involved in the processing of tactile and painful stimuli can be activated by ipsilateral pathways directly from the periphery. The tactile-evoked ipsilateral S1 activation may be due to subcortical reorganization, since it was not observed in the normal subjects.

Adult↗

Tactile directional sensibility: peripheral neural mechanisms in man.

Tactile directional sensibility, i.e. the ability to tell the direction of an object's motion across the skin, is an easily observed sensory function that is highly sensitive to disturbances of the somatosensory system. Based on previous psychophysical experiments on healthy subjects it was concluded that directional sensibility depends on two kinds of information from cutaneous mechanoreceptors; spatio-temporal information and information about friction-induced changes in skin stretch. In the present study responses to similar probe movements as in the psychophysical experiments were recorded from human single mechanoreceptors in the forearm skin. All slowly adapting type 2 (SA2) units were spontaneously active, and with increasing force of friction their discharge rates were modified by probe movements at increasing distances from the Ruffini end-organ, reflecting the high stretch-sensitivity of these units. Slowly adapting type 1 (SA1) and field units responded to the moving probe within well-defined skin areas directly overlying the individual receptor terminals, and compared to the SA2 units their response properties were less dependent on the force of friction. The results suggest that SA1 and field units have the capacity to signal spatio-temporal information, whereas a population of SA2 units have the capacity to signal direction-specific information about changes in lateral skin stretch.

Adult↗

Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin.

Impulses were recorded from unmyelinated afferents innervating the forearm skin of human subjects using the technique of microneurography. Units responding to innocuous skin deformation were selected. The sample (n = 38) was split into low-threshold units (n = 27) and high-threshold units (n = 11) on the basis of three distinctive features, i.e., thresholds to skin deformation, size of response to innocuous skin deformation, and differential response to sharp and blunt stimuli. The low-threshold units provisionally were denoted tactile afferents on the basis of their response properties, which strongly suggest that they are coding some feature of tactile stimuli. They exhibited, in many respects, similar functional properties as described for low-threshold C-mechanoreceptive units in other mammals. However, a delayed acceleration, not previously demonstrated, was observed in response to long-lasting innocuous indentations. It was concluded that human hairy skin is innervated by a system of highly sensitive mechanoreceptive units with unmyelinated afferents akin to the system previously described in other mammals. The confirmation that the system is present in the forearm skin and not only in the face area where it first was identified suggests a largely general distribution although there are indications that the tactile C afferents may be lacking in the very distal parts of the limbs. The functional role of the system remains to be assessed although physiological properties of the sense organs invite to speculations that the slow tactile system might have closer relations to limbic functions than to cognitive and motor functions.

Adult↗

Remarkable capacity for perception of the direction of skin pull in man.

We determined the ability to appreciate the direction of a skin pull caused by a moving pin that was glued to the forearm skin. A majority of the subjects were able to tell the direction of pin movements with an excursion of 0.13 mm (>/=66% correct responses, p<0.05). Local skin anaesthesia showed that stretch sensitive receptors located over 15 mm in front and behind the pin correctly signalled the direction of these minute skin pulls. It was concluded that information about patterns of skin stretch is an important component of the somatosensory system that may contribute not only to kinaesthetic, but also to cutaneous sensations.

Adult↗

Directional sensibility for quantification of tactile dysfunction.

Examination of tactile directional sensibility, i.e., the ability to tell the direction of an object's motion across the skin, has been recommended by several authors for examination of patients with somatosensory disorders. Recent findings about the physiological mechanisms underlying directional sensibility suggested possibilities to further improve the test. In the present investigation a test was constructed that allowed a semiquantification of the directional sensibility of six body areas within 20 min. Normal values were obtained by testing healthy subjects (n = 40), and the normal values were compared to those obtained in a group of patients with tactile symptoms (n = 20). Ten of the patients had abnormal sensory conduction in one or several nerves, and they also had abnormal directional sensibility. Hence, examination of directional sensibility, according to the present protocol, provides a semiquantitative test that appears to be as sensitive as electrophysiological measurement of conduction in detecting dysfunction in tactile nerves.

Adult↗

Receptive field characteristics of tactile units with myelinated afferents in hairy skin of human subjects.

1. Impulses in single nerve fibres from the lateral antebrachial cutaneous nerve were recorded using the microneurography technique in human subjects. 2. In a sample of fifty-five mechanoreceptive units with fast-conducting nerve fibres, five types were identified, i.e. SAI (slowly adapting type I, Merkel), SAII (slowly adapting type II, Ruffini), hair units, field units and Pacinian-type units. The latter three unit types were all rapidly adapting. 3. The detailed structure of thirty-five receptive fields of SAI, SAII, hair and field units was explored with a method which was objective and independent of the experimenter's skill and experience. A lightweight probe was used to scan the receptive field area in a series of tracks 0.23 mm apart while single-unit activity was recorded. 4. SAI fields were small and composed of two to four well-separated high-sensitivity spots and often, in addition, one minor spot of lower sensitivity. SAII units typically fired spontaneously at a low and regular rate. Most fields consisted of one single spot of high sensitivity with diffuse borders. The hair units innervated ten to thirty-three (or more) hairs, which were evenly distributed over a large area. The field units were characterized by a number of small and closely packed high-sensitivity spots with diffuse borders. A conservative estimate indicated eleven spots per unit. 5. The findings indicate that the sheet of mechanoreceptors on the skin of the forearm is distinctly different from that on the dorsum of the hand and in the face. It seems reasonable to assume that the former is more representative for the hairy skin covering the main parts of the body.

Adult↗

Spatial cues serving the tactile directional sensibility of the human forearm.

1. Tactile directional sensibility is considered to rely on the parallel processing of direction-contingent sensory data that depend on skin stretching caused by friction, and spatial cues that vary with time. A temperature-controlled airstream stimulus that prevented the activation of stretch receptors was used to investigate directional sensibility for the skin of the forearm. 2. The dependence on contact load and distance of movement was determined for normal subjects with a two-alternative forced-choice method. Testing was performed under two conditions, elbow bent or straight. Bracing the skin by straightening the arm did not alter the accuracy of the directional sensibility, in contrast to previous findings with stimuli that caused friction. 3. The accuracy of directional sensibility was correlated linearly to the logarithm of the distance of movement of the air jet. No correlation was found between accuracy and contact load, unlike findings with stimuli that cause friction. 4. Measurements were made with different subjects to determine the threshold distance at constant load. On average, subjects were able to distinguish direction with movements of < or = 8 mm. This acuity is sharper than has been reported with static stimuli. There was no correlation between subjects' threshold distances for judging direction and spatial acuity measured with absolute point localization. 5. The ability to distinguish direction was poor for the airstream stimulus compared with stimuli causing frictional contact with hairy skin. Nevertheless, the present findings are consistent with the suggestion that cutaneous spatial acuity is better for dynamic than for static stimuli.

Adult↗

The influence of spatial summation on human tactile directional sensibility.

Spatial summation is known to influence the magnitude of sensation for stationary cutaneous stimuli. Yet analysis of moving stimuli may also be pertinent, since most stimuli that attract our attention involve movements over the skin surface. The present investigation dealt with the importance of spatial summation for the appreciation of the direction of motion for moving stimuli. The ability to detect the direction of motion was tested on the radial surface of the forearm with the two-alternative forced-choice method. Stimulation was performed with a rolling wheel, in order to exclude friction-generated activation of stretch receptors. Each subject was tested with two wheels with the same radius but different widths, 1 mm and 15 mm. On average, the subjects performed better with the wide wheel than with the narrow one for stimulation distances > or = 16 mm. This value also probably exceeds the threshold distance for directional discrimination for the narrow wheel, which indicates that spatial summation improves suprathreshold performance.

Adult↗

A system of unmyelinated afferents for innocuous mechanoreception in the human skin.

It is generally held that tactile mechanisms in the human skin are served by fast-conducting myelinated nerve fibres, whereas touch-sensitive afferents with unmyelinated axons are lacking in man, in contrast to other mammals. In the present study we found evidence that sensitive mechanoreceptive afferents with unmyelinated fibres are quite common and widespread in the hairy skin of human subjects. Their biological role remains an enigma which might attract more attention now that their existence in man has been demonstrated.

Afferent Pathways↗